We hypothesize that interstitial cystitis (IC) and vulvar vestibulitis are local genitourinary manifestations of a systemic syndrome characterized by central nervous system (CNS) dysregulation, both at the spinal and supraspinal levels. This CNS dysregulation is characterized by a) centrally mediated autonomic dysfunction that leads to smooth muscle dysmotility, b) diffusely increased peripheral and visceral nociception (pain sensitivity), and c) a neurogenically mediated inflammatory response. The specific aims: 1) To show that IC and vulvar vestibulitis are local manifestations of a systemic disorder, we will show that there is substantial clinical overlap between these two syndromes and fibromyalgia. Fibromyalgia is a CNS- mediated systemic disorder which affects 2 - 6% of the population, and is characterized by widespread pain, fatigue, and a variety of other symptoms. These 3 conditions have nearly identical demographics, clinical features, and efficacious therapies. We will perform a clinical epidemiologic study to examine a cohort of individuals presenting with pelvic pain and urinary symptoms to assess the prevalence of each of these 3 disorders. 2) To further demonstrate that the bladder and vulvar region are the target tissues in a CNS-mediated disease, we will also concurrently study a number of physiologic and biochemical variables in IC, vulvar vestibulitis, and fibromyalgia (compared to a control group), including: a) Centrally mediated autonomic function. We will utilize Holter monitoring and tilt table testing to examine the central nervous system contribution to autonomic tone. We will demonstrate that all 3 entities are characterized by centrally mediated dysautonomia, and that this is responsible for smooth muscle dysmotility. b) Peripheral nociception. We will utilize a dolorimeter (a pressure gauge) to measure pain threshold and tolerance in all four groups. We will show that patients with IC and vulvar vestibulitis are similar to those with fibromyalgia, in that they display diffusely increased nociception, rather than pain localized to the bladder or vulvar region. c) Visceral nociception. We will likewise demonstrate that all of these disorders are characterized by increased visceral nociception. The finding of concurrently increased peripheral and visceral nociception will confirm that this phenomenon is mediated centrally, at either the spinal or supraspinal level. 3) To show that the inflammatory response in interstitial cystitis is neurogenically mediated. We feel that CNS hyperactivity leading neuropeptide release initiates the inflammatory response in IC. To prove this postulate, we will examine the cellular constituents of urine, post- distension urinary concentration of neuropeptides, and the nature of the inflammatory response to biopsy tissue. In addition, we will perform studies which will show a random or polyclonal expression of T-cell receptors of lymphocytes in IC, which differs from the restricted (oligoclonal or antigen-specific) response that is characteristically seen if initiated by an antigen (e.g. toxin or protein from urine), or as occurs as part of a systemic autoimmune disease.